Journal of Gastrointestinal Oncology,
Год журнала:
2023,
Номер
14(2), С. 1064 - 1076
Опубликована: Апрель 1, 2023
A
significant
desmoplastic
response,
particularly
in
the
fibroblasts,
is
a
characteristic
of
pancreatic
ductal
adenocarcinoma
(PDAC).
Increasing
evidence
has
shown
that
cancer-associated
fibroblasts
(CAFs)
assist
tumor
development,
invasion,
and
metastasis
PDAC.
However,
CAFs-derived
molecular
determinants
regulate
mechanisms
PDAC
have
not
been
fully
characterized.The
expression
microRNA
125b-5p
(miR-125b-5p)
Pancreas
Cancer
(PC)
tissue
para-cancerous
normal
was
examined
using
Polymerase
Chain
Reaction
(PCR).
Cell
counting
kit-8
(CCK8),
wound
healing,
transwell
experiments
were
utilized
to
assess
effect
miR-125b-5p.
Using
cell
luciferase
activity
test
bioinformatics,
it
demonstrated
miR-125b-5p
may
bind
3'-untranslated
region
(3'-UTR)
adenomatous
polyposis
coli
(APC),
thereby
limiting
progression
cancer.PDAC
cells
are
prompted
proliferate,
undergo
epithelial-mesenchymal
transition
(EMT),
spread.
Importantly,
CAFs
release
exosomes
into
cells,
which
significantly
increase
level
those
cells.
Meanwhile,
cancer
lines
tissues
considerably
higher
expression.
MiR-125b-5p's
elevated
mechanically
suppresses
APC
accelerates
spread
cancer.Exosomes
released
by
promote
growth,
metastasis.
Exosomal
inhibition
offers
an
alternate
strategy
for
combating
basic
malady
Diet
is
a
robust
entrainment
cue
that
regulates
diurnal
rhythms
of
the
gut
microbiome.
We
and
others
have
shown
disruption
circadian
clock
drives
progression
colorectal
cancer
(CRC).
While
certain
bacterial
species
been
suggested
to
play
driver
roles
in
CRC,
it
unknown
whether
intestinal
impinges
on
microbiome
accelerate
CRC
pathogenesis.
To
address
this,
genetic
clock,
an
Apc-
driven
mouse
model
was
used
define
impact
When
combined
with
metagenomic
sequencing
identified
dysregulation
many
genera
including
Bacteroides
,
Helicobacter
Megasphaera.
identify
functional
changes
microbial
pathways
dysregulated
nucleic
acid,
amino
carbohydrate
metabolism,
as
well
barrier
function.
Our
findings
suggest
microbiota
composition
permeability
may
contribute
Abstract
The
circadian
clock
coordinates
the
daily
rhythmicity
of
biological
processes,
and
its
dysregulation
is
associated
with
various
human
diseases.
Despite
direct
targeting
rhythmic
genes
by
many
prevalent
World
Health
Organization
(WHO)
essential
drugs,
traditional
approaches
can't
satisfy
need
explore
multi‐timepoint
drug
administration
strategies
across
a
wide
range
drugs.
Here,
droplet‐engineered
primary
liver
organoids
(DPLOs)
are
generated
characteristics
in
4
days,
developed
Chronotoxici‐plate
as
an
vitro
high‐throughput
automated
tool
for
chronotherapy
assessment
within
7
days.
Cryptochrome
1
(
Cry1
)
identified
marker
DPLOs,
providing
insights
rapid
organoid
rhythmicity.
Using
oxaliplatin
representative
drug,
time‐dependent
variations
demonstrated
toxicity
on
Chronotoxici‐plate,
highlighting
importance
considering
effects.
Additionally,
role
chronobiology
underscored
modeling.
This
study
may
provide
tools
both
precision
chronotoxicity
development
optimizing
timing.
Nature Communications,
Год журнала:
2024,
Номер
15(1)
Опубликована: Июль 1, 2024
Abstract
Circadian
gene
expression
is
fundamental
to
the
establishment
and
functions
of
circadian
clock,
a
cell-autonomous
evolutionary-conserved
timing
system.
Yet,
how
it
affected
by
environmental-circadian
disruption
(ECD)
such
as
shiftwork
jetlag
are
ill-defined.
Here,
we
provided
comprehensive
comparative
description
male
liver
expression,
encompassing
transcriptomes,
whole-cell
proteomes
nuclear
proteomes,
under
normal
after
ECD
conditions.
Under
both
conditions,
post-translation,
rather
than
transcription,
dominant
contributor
functional
outputs.
After
ECD,
post-transcriptional
post-translational
processes
major
contributors
or
proteome,
respectively.
Furthermore,
re-writes
rhythmicity
64%
transcriptome,
98%
proteome
95%
proteome.
The
re-writing,
which
associated
with
changes
regulatory
cis-elements,
RNA-processing
protein
localization,
diminishes
regulation
fat
carbohydrate
metabolism
persists
one
week
ECD-recovery.
Journal of Biological Rhythms,
Год журнала:
2025,
Номер
unknown
Опубликована: Янв. 8, 2025
Circadian
disruption
is
pervasive
in
modern
society
and
associated
with
increased
risk
of
disease.
Chronic
jet
lag
paradigms
are
popular
experimental
tools
aiming
to
emulate
human
circadian
experienced
during
rotating
night
shift
work.
induces
metabolic
phenotypes
tied
liver
systemic
functions,
yet
lack
a
clear
definition
for
how
rhythmic
physiology
impaired
under
these
conditions
hinders
the
ability
identify
underlying
molecular
mechanisms.
Here,
we
compared
2
common
chronic
found
that
neither
induced
arrythmicity
each
had
distinct
effects
on
rhythmicity.
Instead,
more
frequent
8-h
forward
shifts
light
schedule
severe
misalignment
non-fasted
hyperglycemia.
Every
other
day
eventually
uncoupled
behavioral
hepatic
rhythms
from
cycle,
reminiscent
free-running
conditions.
These
results
point
misalignment,
not
arrhythmicity,
as
initial
disturbance
dysfunction
environmental
highlight
considerations
interpretation
design
studies.
Research Square (Research Square),
Год журнала:
2025,
Номер
unknown
Опубликована: Апрель 10, 2025
Abstract
Fibrosis,
characterized
by
excessive
extracellular
matrix
(ECM)
accumulation
and
fibroblast
proliferation,
significantly
contributes
to
global
morbidity
mortality,
affecting
millions
worldwide.
Despite
its
prevalence,
the
mechanisms
underlying
fibrotic
skin
diseases
remain
poorly
understood,
effective
treatments
are
scarce.
This
study
leverages
single-cell
RNA
sequencing
(scRNA-seq)
unravel
heterogeneity
of
fibroblasts
in
diseases,
including
normal
skin,
scar,
keloid,
scleroderma.
Through
comprehensive
analysis
scRNA-seq
data
from
public
repositories,
we
identified
distinct
subpopulations
specific
each
condition.
Notably,
pivotal
regulators
for
sub-fibroblast
cluster
were
discovered:
IRF4
CLOCK
RUNX3
scleroderma,
HOXC4
skin.
Further,
was
found
be
predominantly
expressed
keloid
tissues,
with
upregulation
enhancing
proliferation
migration
vitro.
Analysis
The
Cancer
Genome
Atlas
(TCGA)
revealed
that
regulon
genes
upregulated
cutaneous
melanoma
even
more
so
metastatic
tumors.
Our
findings
underscore
utility
dissecting
cellular
complexity
highlight
potential
therapeutic
targets.
not
only
advances
our
understanding
fibrosis
but
also
opens
avenues
targeted
strategies,
moving
closer
personalized
medicine
diseases.
